title: SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization.
abstract: We previously identified a new molecule, "SHATI/NAT8L," which has an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference. Nevertheless, the extent of SHATI localization and its functions are only partially understood. In this study, we used the FLAG-tag method to investigate SHATI localization. We found that SHATI was localized to microtubules when expressed in COS7 cells and cortical primary neurons. This distribution of SHATI was less apparent after cells were treated with colchicine, a tubulin polymerization inhibitor that disrupts the microtubule structure. This finding suggests that SHATI is associated with microtubule structure. Interestingly, overexpression of SHATI in COS7 cells could attenuate the colchicine-induced decrease in acetylated microtubules, indicating that SHATI plays a role in stabilizing microtubules. Furthermore, we showed that Shati deletion impaired neurite elongation. In cortical primary neurons, neurite length and complexity in Shati-knockout (KO) mice were significantly decreased. In pyramidal neurons in the prefrontal cortex, dendrite length and complexity were also significantly decreased in Shati-KO mice compared with wild-type mice. These results suggest a novel function for SHATI, which may be a new member of the microtubule-associated protein family.
authors.affiliation: Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, Japan; The Academic Frontier Project for Private University, Comparative Cognitive Science Institutes, Meijo University, Nagoya, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Toriumi
authors.forename: Miki
authors.initials: M
authors.lastname: Ikami
authors.forename: Mizuki
authors.initials: M
authors.lastname: Kondo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mouri
authors.forename: Takenao
authors.initials: T
authors.lastname: Koseki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ibi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furukawa-Hibi
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Mamiya
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*
chemical_list: D000123:Acetyltransferases; C521704:Shati protein, mouse
keywords: SHATI; colchicin; dendrites; microtubules; neurite outgrowth; tubulin